A. Field of the Invention
The present invention concerns attenuated Francisella bacteria vaccines and methods of preventing and treating a Francisella infection.
B. Background of the Invention
Francisella tularensis is an intracellular Gram negative bacterium that can cause pneumonic tularemia in humans (Ellis et al., 2002; Tarnvik, 1989). F. tularensis subsp. tularensis is classified as one of the most infectious pathogenic bacteria because inhalation with only a few organisms will cause disease and significant mortality (Saslaw et al., 1961). F. tularensis also is considered a potential biological weapon and has been developed as a germ warfare agent by several government programs (Christopher et al., 1997; Dennis et al., 2001; Harris, 1992). Humans infected by F. tularensis usually acquire the disease by contact with infected animals, vectors (ticks), exposure to contaminated food and water, or aerosol exposure (Feldman et al., 2001; Tarnvik, 1989).
To date, F. tularensis live vaccine strain (LVS), which is derived from F. tularensis subspecies holarctica (type B) has been the only vaccine candidate for tularemia. In humans (Saslaw et al., 1961) and in animals (Eigelsbach and Downs, 1961), vaccination with LVS has demonstrated varying degrees of protection against aerosolized and parenteral subsp. tularensis challenges. However, the basis of attenuation of the LVS strain is unknown, making its use in humans somewhat questionable given the uncertain probability of reversion to virulence of the vaccine strain.